epsilon-caproimido pyrimidines



United States Patent 3,410,843 e-CAPROIMIDO PYRIMIDINES Edward W.Pietrusza, Morris Township, Morris County, and Rudolph Pinter,Morristown, N.J., assignors to Allied Chemical Corporation, New York,N.Y., a corporation of New York No Drawing. Continuation-impart ofapplication Ser. No. 188,960, Apr. 20, 1962. This application Mar. 10,1966, Ser. No. 533,235

The portion of the term of the patent subsequent to May 3, 1983, hasbeen disclaimed Claims. (Cl. 260--239.3)

ABSTRACT OF THE DISCLOSURE The present invention relates to thepreparation of the e-caproimido pyrimidines from substituted pyrimidinesand metal salts of e-caprolactam. These pyrimidines are useful inpromoting the polymerization of lactams as described in theabove-mentioned copending application. Particularly outstanding as apromoter is 2,4,6-tri- (e-caproimido) pyrimidine which is a novelcompound.

This application is a continuation-in-part of our copending US.application Ser. No. 188,960, filed Apr. 20, 1962, now U.S. Patent3,249,590.

With the utilization of the promoters of the invention, polymerizationof lactams can be etfected at temperatures below the softening point ofthe resulting polymer. It is well known that in the polymerization ofe-caprolactam, a chemical equilibrium is found between low molecularweight materials and the polymer. At temperatures in excess of thesoftening point of poly-e-caprolactarn, the presence of appreciablequantities of monomeric e-caprolactam and its dimers and trimers ispermitted by the equilibrium, whereas below said temperature theformation of the polymer is more highly favored. Thus the use of ourpromoters obviates purification of the product polymer which is usuallyrequired before a polycaproamide formed at high temperature can beemployed industrially.

In addition, the polycaproamides produced in accord ance with ourinvention contain pyrimido end groups and, accordingly, are inherentlymore stable than, for example, polycaproamides formed by acid catalyststoward oxidation and heat.

We have discovered that the above pyrimidines are produced by heating ametal salt of e-caprolactam and a pyrimidine, i.e., a 1,3-diazine, whichbears on one of its 2-, 4- and -positions a substituent attached by amore electronegative atom than the nitrogen of lactam, hence beingreplaceable by metathesis with the metal salt of e-caprolactam, and onthe remaining carbon atoms of the ring bears such replaceablesubstituent or hydrogen or a substituent inert toward the metal salt ofe-caprolactam.

By metathesis, the metal from the lactam salt combines with thereplaceable substituents present on at least one of the 2-, 4- and6-positions, and the lactam residue replaces said substituents.Substituents replaceable by this metathesis include halogen atoms andsubstituents attached to a carbon atom of the pyrimidine ring by anoxygen atom. Illustrative of such replaceable substituents arez chloro,hydroxy, alkoxy, aryloxy, arylalkoxy, cycloalkoxy, alkylamine,arylamine, arylalkylamino, and alkylamino. Where it is desired to obtainreaction at 3,410,843 Patented Nov. 12, 1968 all of the 2-, 4- and 6-positions in order to prepare a 2,4,6-tri-(e-caproimido) pyrimidine, it"is advantageous to employ as the replaceable substituents chloro,methoxy or phenoxy.

The nitrogen in the 1- and 3-positions on the pyrimidine ring stronglydirect ortho and para substitution while exercising a powerfuldeactivating influence on the 5-position. Therefore, no metathesisoccurs with the sub stituent on the 5-position which is meta-orientedwith respect to both nitrogens, even when this is chloro, phenoxy, orother substituents of the above-described replaceable type.

The promoters can be prepared for the purpose of isolation by heating ina diluent such as benzene a metal salt of the caprolactam and apyrimidine which bears on its carbon atoms substituents chosen in theabovedescribed manner. The metal salt of the e-caprolactam willordinarily be prepared by heating, with e-caprolactam, a strong basesuch as an alkali or alkaline earth metal, including magnesium, orhydride or amide or hydroxide thereof, or the metal oxide or salt of aweak acid. Such reaction is illustrated by the following Equation I:

species of anions are 9 3 and C -CH26 Suitably, the salt-forming metalor compound is admixed under anhydrous conditions with the lactam toform a reaction mixture comprising from about 0.1 to about 1.0,advantageously from about 0.5 to about 0.9 equivalent, of said metal permolecular proportion of lactam. While these ratios of reactants arepreferred, a large excess of lactam can be present. The temperature ofthe mixture is brought to a level at which interaction is completebetween salt-forming metal or compound and the lactam. Suitabletemperatures are in the range from about C. to about C.

The metal salts are relatively stable at temperatures of 20 -25 C. for aperiod of at least one month and even at higher temperatures, e.g., 90C., the time of stability is about four days. Accordingly, the salt canbe prepared and stored if desired.

The addition of a substituted pyrimidine to the caprolactam metal saltproduced by the process illustrated in Equation I results in theformation of an e-caproimido pyrimidine as illustrated by the followingEquation II: N

+ MR1 MR3 MR where M has the meaning given above; R R and R arereplaceable substituents as defined above, and the pyrimidine product isa 2,4,6-tri-(e-caproimido) pyrimidine. As previously discussed, R is notreplaced because of its position on the pyrimidine ring, and it caneither be the same as R or a substituent inert toward metal salts ofcaprolactam such as hydrogen or hydrocarbon groups free of olefinicunsaturation. While the above equation illustrates a reaction where allof R R and R are replaceable substituents, it is to be understood thatany one or any two of these substituents can be inert toward metal saltsof caprolactam, e.g., hydrogen or hydrocarbon groups free of olefinicunsaturation, with the result that no reaction takes place at thecorresponding positions.

The reaction between the substituted pyrimidine and the caprolactammetal salt is carried out in an organic diluent, preferably at atemperature of about 50 C. to 120 C. with particularly good resultsbeing obtained at about 60 C. to 90 C. The diluent employed can be anydry organic compound which under the reaction conditions is liquid anddoes not react with any of the other compounds present. Illustrative ofsuitable diluents are benzene, xylene and toluene. Lactams such ase-caprolactam can also be used as the diluent. However, if it is desiredto isolate the e-CHPI'OiIILldO pyrimidine, care must be taken not toexceed 120 C. and thereby initiate polymerization of the lactam.

The detailed description of our process and the examples which followset forth particularly the employment of lithium hydride and2,4,6-trichloropyrimidine in our process, but it is to be understoodthat these specific compounds and the conditions cited for use therewithare illustrative rather than limiting; and that the same principles andgeneral procedures apply when using other metals or other metalcompounds as defined above and when using other pyrimidine derivatives,including in particular 2,4-dichloropyrirnidine,2,4,6-triphenoxypyrimidine and 2,4-diphenoxypyrimidine, and mixedderivations such as the monochloro-diphenoxy pyrimidines, also likepyrimidines, additionally substituted by one or more inert substituents.Illustrative examples of pyrimidines suitable as starting materials forreaction with lactam salts to form the promoters of our invention are:

2,4,6-trichloropyrimidine 2,4,6-trihydroxypyrimidine (barbituric acid)2,4-dichloropyrimidine 2,4-dibromopyrimidine 2-iodo-6-chloropyrimidine2-chloro-6-fluoropyrimidine 2,4-dihydroxy-6-rnethyl pyrimidine2,4-dihydroxypyrimidine 2-chloro-6-hexoxypyrimidine2,4,6-trimethoxypyrimidine 2,4,6-triphenoxypyrimidine-cyclohexyl-6-bromopyrimidine 2-benzyl-6-chloropyrimidine4-cyclohexyl-6-bromopyrimidine 2,4-di(methylamino) pyrimidine2-bromopyrimidine 2,4-dihexoxypyrimidine 2,4-dibenzyloxypyrimidine2,4-dibenzylan1inopyrimidine 2-chloro-4-butyl-G-methoxypyrimidine2-chloro-4-methyl-fi-decyloxypyrimidine 2-chloro-4,5 -dibutylpyrirnidine4,S-diphenyl-6-chloropyrimidine 2-hydroxypyrimidine2,4-diethoxypyrimidine 2,4-dimethoxypyrimidine or d and

Example A Four liters of distilled, dry xylene and 136 grams (1.2 mols)of distilled, dry caprolactam were introduced into a 5-liter 3-neckedflask, heated with an electric mantle, and equipped with a mechanicalstirrer, reflux condenser, and the necessary gas lines. A dry nitrogenatmosphere was maintained throughout the operation. The solution washeated to 100 C./750 mm. and under a blanket of dry, oxygen-freenitrogen 7.9 grams (1.0 mol) of lithium hydride was added with stirring.Reaction proceeded as indicated by the evolution of hydrogen and theprecipitation of a flocculent solid. The temperature was slowly raisedto 140 C. and with stirring the reaction was allowed to continue for 2hours until the evolution of hydrogen had subsided.

The reaction mixture was cooled to room temperature and filtered under ablanket of dry nitrogen. The isolated precipitate was washed twice with200 cc. of dry, hot benzene and then heated under reduced pressures for24 hours at 8090 C./510 mm. nitrogen. There was obtained grams (92.5%yield) of a white product, melting point 310-340 C. with decomposition,which was found by infrared and elemental analysis to be the lithiumsalt of e-caprolactarn (hygroscopic but stable in air, in absence ofmoisture and carbon dioxide).

The following example is illustrative of our invention and describes aspecific embodiment of our invention, but the invention is not to beinterpreted as limited to all details of the example.

Example Thirty grams of essentially pure lithium salt of ecaprolactam,prepared as in Example A above (0.25 mol), was slurried in dry benzene(500 cc.) and 9.2 grams of 2,4,6-trichloropyrimidine (0.05 mol) wasslowly added under dry nitrogen at 70 C. with stirring. After 2 hours at70 C., the solid residue (excess lithium salt of caprolactam and LiCl)was filtered off. Upon evaporating the benzene at reduced pressure, anoil was obtained to which was added chloroform and ether until aprecipitate formed.

The precipitate was low melting; it was filtered off and the solventswere evaporated from the filtrate to leave a viscous oil whichcrystallized on standing.

It was recrystalized from n-heptane and showed melting point of 148-154C. Analysis for carbon, hydrogen and nitrogen closely checked thetheoretical for substitution of the three chlorine atoms by threecaprolactam residues, e.g. for 2,4,6-tri-(e-caproimido) pyrimidine.Infrared examination confirmed this identification showing absorptionbands -for the pyrimidine and e-caprolactam moieties and absence ofbands for chloro-substituents.

We claim:

1. Process for preparing an (e-caproimido) pyrimidine which comprisesmixing together a metal salt of e-caprolactam, wherein said metal is analkali metal or an alkaline earth metal, and a pyrimidine which bears onone of its 2-, 4- and 6-positions a substituent attached by a moreelectronegative atom than the nitrogen of e-CfiPIO- lactam andreplaceable by metatheses with the metal salt of e-caprolactam, and onthe remainder of its carbon atoms bears such replaceable substituent orhydrogen or a substituent inert toward the metal salt of e-caprolactam.

2. Process of claim 1, wherein the substituted pyrimidine is added to analkali metal salt of e-caprolactam slurried in a dry, inert diluent andmaintained under a dry, inert atmosphere at a temperature of about 120C.

3. Process of claim 2, wherein the metal salt is the lithium salt ofe-caprolactam.

4. Process of claim 1, wherein said pyrimidine has substituents on the2-, 4- and 6-positions which are selected from the group consisting ofchloro, methoxy and phenoxy.

5. The compound 2,4,6-tri-(e-caproimido) pyrimidine.

References Cited UNITED STATES PATENTS 3,249,590 5/1966 Pietrusza et al.260-2393 HENRY R. JILES, Primary Examiner.

R. T. BOND, Assistant Examiner.

